A5074399476- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Adenosine and Purinergic Signaling
- Pharmacological Receptor Mechanisms and Effects
- Neuroscience and Neuropharmacology Research
- Cannabis and Cannabinoid Research
- Neuroscience of respiration and sleep
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurotransmitter Receptor Influence on Behavior
- Connexins and lens biology
- Biochemical effects in animals
- Pediatric Pain Management Techniques
- Nerve injury and regeneration
- Pain Management and Placebo Effect
- Zebrafish Biomedical Research Applications
- Neuroendocrine regulation and behavior
- Sleep and Wakefulness Research
- Prenatal Substance Exposure Effects
- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Stress Responses and Cortisol
- Neurobiology and Insect Physiology Research
- Heme Oxygenase-1 and Carbon Monoxide
- Pain Management and Opioid Use
- Veterinary Pharmacology and Anesthesia
University of Calgary
2016-2025
Saint Louis University
2020
National Institute of Diabetes and Digestive and Kidney Diseases
2020
National Institutes of Health
2020
University of Arizona
2020
University of Messina
2020
The University of Adelaide
2020
University of California, San Diego
2020
Allen Institute for Brain Science
2017-2019
Hospital for Sick Children
2006-2013
Microglia in the dorsal horn of spinal cord are increasingly recognized as being crucial pathogenesis pain hypersensitivity after injury to a peripheral nerve. It is known that P2X4 purinoceptors (P2X4Rs) cause release brain-derived neurotrophic factor (BDNF) from microglia, which necessary for maintaining nerve injury. However, there critical gap understanding how activation microglial P2X4Rs leads BDNF. Here, we show stimulating with ATP evokes biphasic BDNF microglia: an early phase...
Microglia-neuron signalling in the spinal cord is a key mediator of mechanical allodynia caused by peripheral nerve injury. We recently reported sex differences microglia pain mice: mechanisms underlying injury-induced are microglial dependent male but not female mice. Whether this difference hypersensitivity conserved other species unknown. Here, we show that rats, males differ from those females, with P2X4 receptors (P2X4Rs) being point divergence. In injury produced comparable and...
Highlights•Macrophages persist in the injured nerve rodents and humans•Macrophages regulate Schwann cells conduction velocity post-injury•Macrophages have a complex transcriptional profile•Macrophage-derived Gas6 regulates cell maturationSummaryPro-regenerative macrophages are well known for their role promoting tissue repair; however, specific roles regeneration of not defined. Specifically, how interact with following injury during remyelination has been largely unexplored. We demonstrate...
Pain is a multidimensional experience and negative affect, or how much the pain “bothersome”, significantly impacts sufferers' quality of life. It well established that κ opioid system contributes to depressive dysphoric states, but whether this affect precipitated by occurrence chronic remains tenuous. Using model persistent pain, we show quantitative real-time-PCR, florescence in situ hybridization, Western blotting GTPgS autoradiography an upregulation expression function receptors (KORs)...
Background and Purpose Cannabinoids are a promising therapeutic avenue for chronic pain. However, clinical trials often fail to report analgesic efficacy of cannabinoids. Inhibition voltage gate calcium (Ca v ) channels is one mechanism through which cannabinoids may produce analgesia. We hypothesized that cannabinoid receptor agonists target different types Ca distinct mechanisms. Experimental Approach Electrophysiological recordings from tsA‐201 cells expressing either 3.2 or 2.2 were used...
The innate immune system modulates opioid-induced effects within the central nervous and one target that has received considerable attention is toll-like receptor 4 (TLR4). Here, we examined contribution of TLR4 in development morphine tolerance, hyperalgesia, physical dependence two inbred mouse strains: C3H/HeJ mice which have a dominant negative point mutation Tlr4 gene rendering non-functional, B10ScNJ are null mutants. We found neither acute antinociceptive response to single dose...
Tolerance to the analgesic effects of opioids is a major problem in chronic pain management. Microglia are implicated opioid tolerance, but core mechanisms regulating their response remain obscure. By selectively ablating microglia spinal cord using saporin-conjugated antibody Mac1, we demonstrate causal role for development, not maintenance, morphine tolerance male rats. Increased P2X7 receptor (P2X7R) activity cardinal feature microglial activation, and this study found that potentiates...
Abstract Dopamine is well known to regulate movement through the differential control of direct and indirect pathways in striatum that express D 1 2 receptors respectively. The spinal cord also expresses all dopamine receptors; however, how specific network output mammals poorly understood. We explore receptor-specific mechanisms underlie dopaminergic neonatal mice during changes excitability. During spontaneous activity, which a characteristic developing networks operating low excitability...
Treating chronic pain by using opioids, such as morphine, is hampered the development of opioid-induced hyperalgesia (OIH; increased sensitivity), antinociceptive tolerance, and withdrawal, which can contribute to dependence abuse. In central nervous system, purine nucleoside adenosine has been implicated in beneficial detrimental actions but extent their interaction remains poorly understood. Here, we demonstrate that morphine-induced OIH tolerance rats associated with a twofold increase...
The recent identification of novel cellular substrates opioid withdrawal that are blocked by clinically approved drugs brings the promise much needed new therapies.
Cannabis edibles are an increasingly popular form of cannabis consumption. Oral consumption has distinct physiological and behavioral effects compared with injection or inhalation. An animal model is needed to understand the pharmacokinetics oral in rodents as a for human edible use.Adult male female C57BL/6 mice received single dose commercially available oil (5 mg/kg Δ⁹-tetrahydrocannabinol [THC]) by gavage. At 0.5, 1, 2, 3, 6 hours post exposure, plasma, hippocampus, adipose tissue were...
The ventrolateral periaqueductal gray (vlPAG) functionally projects to diverse brain regions, including the locus coeruleus (LC). Excitatory projections from vlPAG LC are well described, while few studies have indicated possibility of inhibitory projections. Here, we quantified relative proportion excitatory and vlPAG-LC in male female mice, found an unexpected overlapping population neurons expressing both GAD2 VGLUT2. Combined